Dimethyl Cuprate Research Articles

Conjugate Additions of Me2CuLi to Enantiopure γ-Hydroxy-δ-sulfinyl and Sulfonyl Pentenoates

[reaction: see text] A systematic study of dimethyl cuprate conjugate additions to diastereoisomeric ethyl gamma-hydroxy (or tert-butyldimethylsilyloxy)-delta-p-tolylsulfinyl-2-pentenoates and the analoguous sulfones showed mainly 3,4-anti diastereoselectivity when the reaction occurred in the presence of TMSCl. The pi-facial diastereoselection is mainly governed by the gamma-hydroxy or silyloxy group, whereas the role of the sulfur functionality is to increase the reactivity of the pentenoate system, probably by assisting the transfer of the alkyl group from the cuprate. This was evidenced by the reactions on similar systems that lack the sulfur functions. The appropriate choice of NH4OH or HCl hydrolysis in the workup allowed direct access to the open chain products or the lactones.

Dimethyl cuprate undergoes C-C bond coupling with methyliodide in the gas phase but dimethyl argenate does not.

Multistage mass spectrometry experiments have been used to synthesize and study the reactions of (CH3)2M-(M = Cu and Ag) with methyl iodide in the gas phase. While the dimethylcuprate ion (M = Cu) reacts with CH3I via C-C bond cross coupling, its silver congener is unreactive. The experimental results are consistent with MP2/6-31++G** ab initio calculations, which reveal that the preferred mechanism for Cu involves the formation of a T-shaped Cu transition state. [reaction: see text]

Synthesis of trichiliasterones A and B — 16-Ketosteroids isolated from Trichilia hirta and Trichilia americana

The syntheses of trichiliasterone A (3β-hydroxypregnan-2,16-dione) and trichiliasterone B (2-hydroxyandrost-1,4-diene-3,16-dione) have been carried out starting from isoandrosterone and testosterone acetate, respectively. In each synthesis the functionality in the D ring was installed prior to working on ring A. In the case of trichiliasterone A, the D ring chemistry involved a Wittig reaction to generate the 17-methylene group, followed by SeO2 oxidation to give an α,β-unsaturated ketone. Reaction with lithium dimethyl cuprate gave the required 17-ethyl-16-keto functionality. A 2,3-epoxy enol acetate served as the key intermediate for the generation of the 2-keto-3-hydroxy functions in ring A. The transposition of the keto function from C-16 to C-17 in the synthesis of trichiliasterone B was accomplished via oxymercuration–demercuration of the Δ16—17 double bond followed by oxidation. The hydroxyl group at C-2 and the additional ring A unsaturation were introduced by lead tetra-acetate treatment of the 3-keto-4-enone function and subsequent air oxidation.Key words: 16-ketosteroids, plant steroids, Trichilia hirta, trichiliasterones.

Synthesis and structure of the chromiumcarbonyl complexed phenyl allene

The chromiumtricarbonyl complexed phenyl allene 4 can be readily synthesized by palladium catalyzed hydride reduction or dimethyl cuprate mediated reduction of suitable propargyl ester derivatives 3 and 5. This parent compound of chromiumcarbonyl complexed aryl allenes is fairly stable and is unambiguously characterized by an X-ray structure analysis. Thiolate adds to 4 to give a 3.5:1 distribution between the nonconjugated and the conjugated addition products 7 and 8 in good yield.

Stereoselective synthesis of precursors of the macrolide antibiotics via reactions of sulfur ylides with chiral aldehydes

Reactions of stabilized sulfur ylides with chiral aldehydes provided epoxides with high stereoselectivity. The opening of the resulting epoxides with lithium dimethyl cuprate gave 2-methyl-3-hydroxy amides which represent potentially useful building blocks for the synthesis of macrolide natural products. These amides were transformed into chiral aldehydes, with a methyl group in the α-position, and were reacted, in a iterative process, with a sulfur ylide reagent to give, in high yield and stereoselectivity, the epoxides with the stereochemistry according to Felkin-Ahn control. Finally, opening of the epoxide with the Gilman reagent provided a compound with four stereocenters occurring in the macrolide-type of natural products.

Preparation of alkyl 3-methylalka-2,4-dienoates from γ,δ-unsaturated β-keto esters via the corresponding conjugated unsaturated 3-enol phosphates

Methylation of α,β,γ,δ-unsaturated-β-substituted enol phosphates with lithium dimethyl cuprate gave a mixture of (2 E,4 E)- and (2 Z,4 E) alkyl 3-methylalka-2,4-dienoates and unsubstituted alkyl alka-2,4-dienoates. An improved synthesis is described for ethyl β-safranate and the insect growth regulator hydroprene.

Reaction of lithium dimethyl cuprate with carbonyl iron α,β-unsaturated ketone complexes: the structure of a novel η3, η3-[(196-diphenyl)-3,4-(distyr-1-yl)-1,3,5-hexatriene]-Fe(CO) 2 complex

The reaction between η 4- α, β-unsaturated ketene-Fe(CO) 3 complexes and Me 2CuLi in the absence of CO atmosphere yields the corresponding η 4-vinylketene complexes 2, 4 and 6. The reaction between η 2-dibenzylideneacetone-Fe(CO) 4 and Me 2CuLi gives a new dimeric complex 8, which was characterized by mass spectrometry, IR, 1H and 13C NMR spectroscopy and its structure confirmed by single-crystal X-ray analysis.

Structural Characterization of Organocopper Complexes by EXAFS and XANES: Evidence that Cyanide Does Not Coordinate to Cu in Dimethyl Cuprate Solutions

While there are no crystallographically characterized examples of {pi}-only coordinated cyanides, such a species would lack the second shell EXAFS from Cu{hor_ellipsis}N (CuC{equivalent_to}N) scattering and thus might be consistent with published data. Lipschutz and James suggest that EXAFS {open_quotes}has not been rigorously proven for tri- and tetracoordinate Cu(I) species{close_quotes} which, while not true in general, is true for organocuprate reagents. In this communication, we provide a direct test of cyanide {pi}-coordination to R{sub 2}CuLi. 2 figs., 1 tab.

ChemInform Abstract: Stereochemical Aspects of the Hydroalumination‐Iodination of α‐ Enyne Alcohols and Methylation of the Derivatives of 3‐Iodo‐2,4‐ alkyldiene‐1‐ol with Lithium Dimethyl Cuprate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantiomerically pure dimethyl (2S)-N-(9-phenylfluoren-9-yl)-3,4-didehydroglutamate as chiral educt. Chirospecific synthesis of (+)-5-O-carbamoylpolyoxamic acid and 3-alkylglutamates

We report here a short and efficient synthesis (four steps, 78% overall yield) of dimethyl (25)-N-(9-phenylfluoren-9-yl)-3,4-didehydroglutamate (1) in enantiomerically pure form from L-glutamic acid. The C-C double bond in 1 was introduced by selective selenenylation-oxidation of dimethyl N-(9-phenylfluoren-9-yl)glutamate. 1 did not undergo loss of enantiomeric purity when stored for several weeks at room temperature, thus demonstrating the ability of the 9-phenylfluoren-9-yl (Pf) group to protect the highly acidic chiral center of 1 from racemization. The α,β-unsaturated carboxyl group of 1 was selectively reduced with DIBAL. Carbamoylation of the resulting alcohol, followed by OsO 4 -mediated hydroxylation of the double bond and deprotection afforded (+)-5-O-carbamoylpolyoxamic acid, a component of the polyoxin family of antifungal antibiotics ( >40% overall yield from glutamic acid). 1 underwent lithium dimethyl cuprate addition with complete retention of chiral integrity, albeit in a nonstereoselective fashion, to give 3-methylglutamates and 3-methylpyroglutamates

ChemInform Abstract: Synthesis of (1R,4R,7S)‐ and (1S,4S,7S)‐2‐(4‐Tolylsulfonyl)‐5‐ phenylmethyl‐7‐methyl‐2,5‐diazabicyclo(2.2.1)heptanes via Regioselective Opening of 3,4‐Epoxy‐D‐proline with Lithium Dimethyl Cuprate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of (1R,4R,7S)‐ and (1S,4S,7S)‐2‐(4‐tolylsulfonyl)‐5‐phenyl‐methyl‐7‐methyl‐2,5‐diazabicyclo[2.2.1]heptanes via regioselective opening of 3,4‐epoxy‐d‐proline with lithium dimethyl cuprate

AbstractThe synthesis of (1S,4S,7S)‐ and (1R,4R,7S)‐2‐(4‐tolylsulfonyl>5‐phenylmethyl‐7‐rnethyl‐2,5‐diazabicyclo‐[2.2.1]heptanes (20) and (22) from trans 4‐hydroxy‐L‐proline is described.

Synthesis and reactivity of tricarbonyl(η 5-4-triethylsilyl-1methylpentadienyl) iron(+1) cation

Tricarbonyl(η 5-4-triethylsilyl-1-methylpentadienyl)iron(+1) hexafluorophosphate was prepared by the protonation of γ- endo tricarbonyl (η 4-5-triethylsilyl-3,5-hexadien-2-ol)iron with hexafluorophosphoric acid. The cation reacts with H 2O, CH 3OH, NaBH 3CN, PPh 3, sodium dimethylmalonate and dimethyl cuprate in a regiospecific fashion by nucleophilic attack at C1. The regioselectivity for nucleophilic attack appears to be predominantly the result of steric control.

Cyclopentannulation reactions with organoiron reagents. Facile construction of functionalized hydroazulenes

Troponeiron tricarbonyl, 2-methyltroponeiron tricarbonyl, and 4-methyltroponeiron tricarbonyl are converted to fluxional tropyliumiron tricarbonyl salts by treatment with either trimethylsilyl or di-n-butylboron triflate. These pentadienyliron cations react with (η 1 -allyl)-, (η 1 -propargyl)-, and (η 1 -allenyl)Fp complexes [Fp=C 5 H 5 Fe(CO) 2 ] to give ketohydroazulene cycloadducts derived, in each reaction, from a single tautomeric tropyllium cation. The further reaction of two such cycloadducts with lithium dimethyl cuprate gave tricyclic ketones, through a sequence depicted as involving initial formation of an anionic acyliron complex, followed by migratory insertion and an intramolecular aldol condensation

ChemInform Abstract: Asymmetric Synthesis of Malic Acid‐Type Synthons via Chiral Norephedrine‐Derived Oxazolidines.

Abstract Polyoxygenated C4 synthons 5-7 are synthesized in enantiomerically pure form starting from ephedrine derived oxazolidines 2,4 and 13. The 1,4-benzylate addition to 2 and 4, the key step in the synthesis of 5 and 6, proceeds cleanly with almost complete diastereoface selection. The key steps in the synthesis of target 7 are the nucleophilic epoxidation of aldehyde 13 and the lithium dimethyl cuprate epoxide opening, both of which proceed with high regio and stereocontrol. This route compares favorably with synthesis from malic acid, in that both enantiomers of ephedrine are available cheaply and it provides three differentiated oxygenated positions directly.

Methodology for the enantioselective synthesis of aldols and other 1,3-dioxygenated systems

The enantioselective synthesis of the spiroenones 3, 4 from(S)-glycidol-O-benzyl ether and lithiated furan derivatives is described. After conjugate addition of lithium dimethyl cuprate or lithium divinyl cuprate and conversion of the resulting saturated ketones to their respective iodides 7 and 8, fragmentation of these halides leads to the formation of acyclic aldol-containing carbon skeletons

Synthesis of ω-labelled fatty acids

A synthetic procedure for producing isotopically ω-labelled fatty acids is described. The isotopic label is introduced by reducing an ω-tosylate with either labelled sodium borohydride or labelled lithium dimethyl cuprate.

Asymmetric synthesis of malic acid-type synthons VIA chiral norephedrine-derived oxazolidines

Polyoxygenated C 4 synthons 5-7 are synthesized in enantiomerically pure form starting from ephedrine derived oxazolidines 2,4 and 13. The 1,4-benzylate addition to 2 and 4, the key step in the synthesis of 5 and 6, proceeds cleanly with almost complete diastereoface selection. The key steps in the synthesis of target 7 are the nucleophilic epoxidation of aldehyde 13 and the lithium dimethyl cuprate epoxide opening, both of which proceed with high regio and stereocontrol. This route compares favorably with synthesis from malic acid, in that both enantiomers of ephedrine are available cheaply and it provides three differentiated oxygenated positions directly.

The hydroalumination-iodination of enyne α-alcohols: Synthesis of 3-methyl-2,4-alkadien-1-ols

It has been found that the reaction course of hydroalumination-iodination using 2-methyl-5-hexen-3yn-2-ol and (6E)-9,13-dimethyl-6,12-tetradecadien-4-yn-3-ol as substrates is ambiguous. The subsequent reaction of lithium dimethyl cuprate with iodo dienols unlike that of iodo alkenols is non-stereoselective. These reactions have been used for the synthesis of a juvenile hormone mimic (4E, 6E)-5,9,13-trimethyl-4,6,12-tetradecatrien-3-ol.

Approaches to higher-carbon sugars, based on the use of sugar-derived, stabilized Wittig reagents

1-(1,2:3,4-Di- O-isopropylidene-α- d-galactopyranuronyl)imidazole, obtained by treating the corresponding diacetal of α- d-galactopyranuronic acid with 1,1-carbonyldiimidazole, reacts with methylenetriphenylphosphorane to give (1,2:3,4-di- O-isopropylidene-α- d-galactopyranuronyl)-(triphenylphosphoranylidene)methane ( 3) as a crystalline, stable Wittig reagent. Compound 3 reacts with aldehydo sugars to provide α,β-unsaturated ketones, preponderantly as the E isomers. The α,β-unsaturated ketones react with lithium dimethyl cuprate to afford an ∼3:1 mixture of the 1,4-addition products, and with methylmagnesium chloride to give a 12:1 mixture of the tertiary allylic alcohols methyl 5-deoxy-5- C-[7-deoxy-1,2:3,4-di- O-isopropylidene-6- C-methyl- d(and l)- glycero-α- d- galacto-heptos-7( E)-ylidene]-2,3- O-isopropylidene-β- d-ribofuranoside, which undergoes an oxidative rearrangement when treated with pyridinium chlorochromate.